Impact of sixteen established pancreatic cancer susceptibility loci in American Jews

Background: The higher risk of pancreatic cancer in Ashkenazi Jews compared with non-Jews is only partially explained by the increased frequency of BRCA1 and BRCA2 mutations in Ashkenazi Jews. Methods: We evaluated the impact of 16 established pancreatic cancer susceptibility loci in a case–control sample of American Jews, largely Ashkenazi, including 406 full-Jewish pancreatic cancer patients and 2,332 full-Jewish controls, genotyped as part of the Pancreatic Cancer Cohort and Case–Control Consortium I/II (PanScan I/II), Pancreatic Cancer Case-Control Consortium (PanC4), and Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) datasets. We compared risk in full-Jewish subjects with risk in part-Jewish; non-Jewish Southern European; and in the combined non-Jewish Eastern, Northern, Southern, and Western European (non-Jewish white European) subjects from the same datasets. Jewish ancestries were genetically identified using seeded Fast principal component analysis. Data were analyzed by unconditional logistic regression, and adjusted for age, sex, and principal components. Results: One SNP on chromosome 13q22.1 (rs9543325; OR, 1.36; 95% confidence interval, 1.16–1.58; P = 10-^4.1) was significant in full-Jews. Individual ORs and minor allele frequencies were similar between Jewish and non-Jewish white European subjects. The average ORs across the 16 pancreatic cancer susceptibility loci for full-Jewish, full- plus part-Jewish, non-Jewish Southern European, and non-Jewish white European subjects were 1.25, 1.30, 1.31, and 1.26, respectively. Conclusions: The 16 pancreatic cancer susceptibility loci similarly impact Jewish and non-Jewish white European subjects, both individually and as summary odds. Impact: These 16 pancreatic cancer susceptibility loci likely do not explain the higher risk seen in Ashkenazi Jews.